Abstract
Alzheimer’s disease is a neurodegenerative disease involving memory impairment, confusion, and behavioural changes. With increasing life expectancy, it is projected that Alzheimer’s disease cases will rise over the coming decades. There is no known cure for Alzheimer’s disease, and the causes of the illness are poorly understood. Some factors that are believed to contribute include the blood brain barrier, inflammation, oxidative stress and epigenetic alterations. Many of these factors are believed to initiate years or decades prior to the clinical onset of Alzheimer’s disease, presenting an obstacle in developing treatments.
Prior studies investigating the effects of oxidative stress on Jurkat T-lymphoma cells have observed DNA methylation changes with relevance to Alzheimer’s disease. The current study aims to expand on these findings by investigating the relationship in cell lines with more relevance to Alzheimer’s disease, including pericytes and mouse embryonic fibroblasts. Pericytes are involved in maintaining the integrity of the blood brain barrier, and mouse embryonic fibroblasts are a widely used cell line that enabled optimisation of the experiment. Both cell types were treated with glycine chloramine, and DNA methylation levels were assessed 24 hours and 72 hours post-treatment using the Illumina Infinium Mouse Methylation 285K Array.
In both cell types, there was no significant difference in DNA methylation changes at either time point, after correction for multiple testing. Analysis of site-specific changes showed that the top significant differentially methylated CpG sites demonstrated a significant change in DNA methylation at 72 hours post-treatment. These CpG sites corresponded with a variety of genes with implications in AD, including Cdh1, Nipsnap2, and Hmgb1. It is hoped that the genetic variants and pathways highlighted in this study can provide direction for future research in AD treatments, such as in precision medicine.